Translation Regulation of Gene Expression in Toxic Dinoflagellates

点击翻译按钮获取中文摘要

A number of dinoflagellate species are known to produce potent neurotoxins. Their blooms are commonly referred to as "red tides". An understanding of the genetic regulatory mechanisms that affect bloom growth and in particular the development of biomarkers to assess bloom growth status are essential for the development of scientifically sound management and mitigation policies. The genetic organization and regulation of these organisms has been shown to be distinct from nonprotist eukaryotes. Dinoflagellates are remarkable for their extremely large genomes that show little transcriptional regulation and with genes present as multiple tandem copies that are polycistronically processed through coupled trans-splicing and polyadenylation. A broad range of investigations has implicated mRNA recruitment as a major site of regulation of gene expression. However, relatively little is understood regarding translational initiation and its regulation in these organisms. In this project, a research team centered at the University of Maryland Institute of Marine and Environmental Technology will attempt to unravel the roles of the likely key players in translational regulation, eIF2 and eIF4, along with the spliced leader cap structures in regulating gene expression. Using the icthyotoxic dinoflagellate, Karlodinium veneficum and the toxin producing Karenia brevis, they will (1) determine whether changes in eIF2á phosphorylation underlie diel changes in gene expression or responses to different stressors; (2) begin characterization of the eIF2á-kinases from K. veneficum; (3) characterize the ability of K.veneficum eIF4E family member to bind to cap structures and translational binding partners; and (4) assess the role of K.veneficum eIF4E members in mRNA recruitment. Given the central role of translation in dinoflagellate gene expression, this should provide significant insight into mechanisms relevant to dinoflagellate growth, toxicity, and the regulation of harmful algal blooms. These results are expected to define a new paradigm for translational regulation in dinoflagellates, thus offering an innovative approach to bridge the gap between genomics and physiological complexity in dinoflagellates. Understanding the mechanism of translational regulation of dinoflagellate gene expression may begin to provide insight into the regulation of toxin production by these organisms and may be of direct use in monitoring/managing harmful algal blooms. Broader Impacts: The studies will provide critical insight into mechanisms relevant to dinoflagellate growth, toxicity, and the regulation of harmful algal blooms, with a long term goal of providing avenues for intervention. The project will provide research experiences/training to high school students, undergraduate interns and area high school teachers. JOINT FUNDING BY NSF AND NIEHS: The original proposal on which this project is based (R01 ES021949-01) was submitted to the National Institutes of Environmental Health Sciences (NIH/NIEHS) in response to Funding Opportunity Announcement RFA-ES-11-013 , "Oceans, Great Lakes and Human Health (R01)", an opportunity jointly sponsored by NSF. This project is cooperatively funded through separate awards from NSF and NIEHS.